Dataset Information

Olfactory functions at the intersection between environmental exposure to manganese and Parkinsonism.

ABSTRACT: The olfactory function can be affected by occupational and environmental exposure to various neurotoxicants that can be transported through the olfactory pathway. Olfactory impairment is a highly recurrent non-motor dysfunction in Parkinson's disease and is considered an early predictive sign of neurodegeneration. Changes in olfactory perception may be caused by a dopaminergic dysregulation, possibly related to changes at the level of dopamine receptors. Manganese is an essential element that can become neurotoxic in various conditions inducing an overload in the organism. Being actively transported through the olfactory tract, manganese can cause impairment of olfactory function and motor coordination in different age groups like children and elderly. Odor and motor changes are interrelated and may be caused by a Mn-induced dopaminergic dysregulation affecting both functions. Given these findings, further research is imperative on the possible role of manganese exposure as a pathogenetic factor for Parkinsonism.

SUBMITTER: Zoni S

PROVIDER: S-EPMC3380137 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Olfactory functions at the intersection between environmental exposure to manganese and Parkinsonism.

Zoni Silvia S Bonetti Giulia G Lucchini Roberto R

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 20120602 2-3

The olfactory function can be affected by occupational and environmental exposure to various neurotoxicants that can be transported through the olfactory pathway. Olfactory impairment is a highly recurrent non-motor dysfunction in Parkinson's disease and is considered an early predictive sign of neurodegeneration. Changes in olfactory perception may be caused by a dopaminergic dysregulation, possibly related to changes at the level of dopamine receptors. Manganese is an essential element that ca ...[more]

PMID: 22664337

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Project description:There is increasing evidence that environmental manganese (Mn) exposure early in life can have negative effects on children's neurodevelopment and increase the risk of behavioral problems, including attention deficit hyperactivity disorder (ADHD). Factors that may contribute to differences in sensitivity to Mn exposure are sex and genetic variation of proteins involved in the regulation of Mn concentrations. Here we investigate if sex and polymorphisms in Mn transporter genes SLC30A10 and SLC39A8 influence the association between Mn exposure and ADHD-related behavioral problems in children. The SNPs rs1776029 and rs12064812 in SLC30A10, and rs13107325 in SLC39A8 were genotyped by TaqMan PCR or pyrosequencing in a population of Italian children (aged 11-14?years; n?=?645) with a wide range of environmental Mn exposure. Mn in surface soil was measured in situ using XRF technology or modeled by geospatial analysis. Linear regression models or generalized additive models (GAM) were used for analyzing associations between soil Mn and neurobehavioral problems assessed by the Conners' behavior rating scales (self-, and parent-reported). Gene-environment interactions (Mn transporter genotype x soil Mn) were evaluated using a genetic score in which genotypes for the three SNPs were combined based on their association with blood Mn, as an indication of their influence on Mn regulation. We observed differences in associations between soil Mn and neurobehavior between sexes. For several self-reported Conners' scales, girls showed U-shaped relationships with higher (worse) Conners' scoring at higher soil Mn levels, and several parent-reported scales showed positive linear relationships between increasing soil Mn and higher Conner's scores. For boys, we observed a positive linear relationship with soil Mn for one Conner's outcome only (hyperactivity, parent-reported). We also observed some interactions between soil Mn and the genetic score on Conner's scales in girls and girls with genotypes linked to high blood Mn showed particularly strong positive associations between soil Mn and parent-reported Conners' scales. Our results indicate that sex and polymorphisms in Mn transporter genes contribute to differences in sensitivity to Mn exposure from the environment and that girls that are genetically less efficient at regulating Mn, may be a particularly vulnerable group.

Project description:Whether environmental exposure to Manganese (Mn) in adults is associated with poorer results in cognitive and motor function is unclear. We aimed to determine these associations through a meta-analysis of published studies. A systematic review was conducted to identify epidemiological studies on a population ≥18 years old exposed to environmental airborne Mn, and in which results on specific tests to evaluate cognitive or motor functions were reported. We consulted Medline through PubMed, Web of Science and SCOPUS databases. We also performed a manual search within the list of bibliographic references of the retrieved studies and systematic reviews. To weight Mn effects, a random effects versus fixed effect model was chosen after studying the heterogeneity of each outcome. Eighteen studies met the inclusion criteria. Among them, eleven studies reported data susceptible for meta-analysis through a pooled correlation or a standardized means difference (SMD) approach between exposed and non-exposed groups. Regarding cognitive function, the results of the studies showed heterogeneity among them (I2 = 76.49%, p < 0.001). The overall effect was a statistically significant negative correlation in the random effects model (pooled r = -0.165; 95%CI: -0.214 to -0.116; p < 0.001). For SMD, the results showed a lower heterogeneity with a negative SMD that did not reach statistical significance under the fixed effects model (SMD = -0.052; 95%CI -0.108 to 0.004; p = 0.068). Regarding motor function, heterogeneity (I2 = 75%) was also observed in the correlation approach with a pooled r (random effect model) = -0.150; 95%CI: -0.219 to -0.079; p < 0.001. Moderate heterogeneity was observed according to the SMD approach (I2 = 52.28%), with a pooled SMD = -0.136; 95%CI: -0.188 to-0.084; p < 0.001, indicating worse motor function in those exposed. Correlation approach results support a negative effect on cognitive and motor functions (the higher the Mn levels, the poorer the scores). Regarding the SMD approach, results also support a worse cognitive and motor functions in those exposed, although only for motor function statistical significance was obtained.

Project description:BackgroundAlthough prior studies showed a correlation between environmental manganese (Mn) exposure and neurodevelopmental disorders in children, the results have been inconclusive. There has yet been no consistent biomarker of environmental Mn exposure. Here, we summarized studies that investigated associations between manganese in biomarkers and childhood neurodevelopment and suggest a reliable biomarker.MethodsWe searched PubMed and Web of Science for potentially relevant articles published until December 31th 2019 in English. We also conducted a meta-analysis to quantify the effects of manganese exposure on Intelligence Quotient (IQ) and the correlations of manganese in different indicators.ResultsOf 1754 citations identified, 55 studies with 13,388 subjects were included. Evidence from cohort studies found that higher manganese exposure had a negative effect on neurodevelopment, mostly influencing cognitive and motor skills in children under 6?years of age, as indicated by various metrics. Results from cross-sectional studies revealed that elevated Mn in hair (H-Mn) and drinking water (W-Mn), but not blood (B-Mn) or teeth (T-Mn), were associated with poorer cognitive and behavioral performance in children aged 6-18?years old. Of these cross-sectional studies, most papers reported that the mean of H-Mn was more than 0.55??g/g. The meta-analysis concerning H-Mn suggested that a 10-fold increase in hair manganese was associated with a decrease of 2.51 points (95% confidence interval (CI), -?4.58, -?0.45) in Full Scale IQ, while the meta-analysis of B-Mn and W-Mn generated no such significant effects. The pooled correlation analysis revealed that H-Mn showed a more consistent correlation with W-Mn than B-Mn. Results regarding sex differences of manganese associations were inconsistent, although the preliminary meta-analysis found that higher W-Mn was associated with better Performance IQ only in boys, at a relatively low water manganese concentrations (most below 50??g/L).ConclusionsHigher manganese exposure is adversely associated with childhood neurodevelopment. Hair is the most reliable indicator of manganese exposure for children at 6-18?years of age. Analysis of the publications demonstrated sex differences in neurodevelopment upon manganese exposure, although a clear pattern has not yet been elucidated for this facet of our study.

Dataset Information

Olfactory functions at the intersection between environmental exposure to manganese and Parkinsonism.

Publications

Olfactory functions at the intersection between environmental exposure to manganese and Parkinsonism.

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